Aluminum (Al) is one of the most common elements in the earth crust and increasingly used in food, consumer products and packaging. Its hazard potential for humans is still not completely understood. Besides the metallic form, Al also exists as mineral, including the insoluble oxide, and in soluble ionic forms. Representatives of these three species, namely a metallic and an oxidic species of Al-containing nanoparticles and soluble aluminum chloride, were applied to human intestinal cell lines as models for the intestinal barrier. We characterized physicochemical particle parameters, protein corona composition, ion release and cellular uptake. Different in vitro assays were performed to determine potential effects and molecular modes of action related to the individual chemical species. For a deeper insight into signaling processes, microarray transcriptome analyses followed by bioinformatic data analysis were employed. The particulate Al species showed different solubility in biological media. Metallic Al nanoparticles released more ions than Al₂O₃ nanoparticles, while AlCl₃ showed a mixture of dissolved and agglomerated particulate entities in biological media. The protein corona composition differed between both nanoparticle species. Cellular uptake, investigated in transwell experiments, occurred predominantly in particulate form, whereas ionic Al was not taken up by intestinal cell lines. Transcellular transport was not observed. None of the Al species showed cytotoxic effects up to 200 µg Al/mL. The transcriptome analysis indicated mainly effects on oxidative stress pathways, xenobiotic metabolism and metal homeostasis. We have shown for the first time that intestinal cellular uptake of Al occurs preferably in the particle form, while toxicological effects appear to be ion-related.

中文翻译：

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含铝纳米材料对人肠道caco-2细胞的吸收及其分子影响

铝（Al）是地壳中最常见的元素之一，并越来越多地用于食品，消费品和包装中。它对人类的潜在危害仍未完全了解。除金属形式外，Al还以矿物质形式存在，包括不溶性氧化物和可溶离子形式。这三种物质的代表，即含铝纳米颗粒的金属和氧化物质以及可溶性氯化铝，被应用到人肠细胞系作为肠屏障模型。我们表征了物理化学粒子参数，蛋白电晕组成，离子释放和细胞摄取。不同的体外进行测定以确定与各个化学物种有关的潜在作用和分子作用方式。为了更深入地了解信号传导过程，采用了微阵列转录组分析，然后进行了生物信息学数据分析。Al颗粒在生物介质中显示出不同的溶解度。金属Al纳米颗粒比Al ₂ O ₃纳米颗粒释放更多的离子，而AlCl ₃在生物介质中显示出溶解的和团聚的颗粒实体的混合物。两种纳米颗粒之间的蛋白质电晕组成不同。在transwell实验中研究的细胞摄取主要以颗粒形式发生，而离子Al并未被肠道细胞系吸收。没有观察到跨细胞运输。最高200 µg Al / mL的Al都没有表现出细胞毒性作用。转录组分析表明主要影响氧化应激途径，异种生物代谢和金属稳态。我们首次表明肠道细胞对铝的吸收最好以颗粒形式发生，而毒理作用似乎与离子有关。